Our first objective is to obtain experimental values of the Zimm-Bragg growth and nucleation parameters, s and o, for each of the 20 naturally occurring amino acids, in water and in organic solvents. These parameters will characterize, in a quantitative way, the tendency of each amino acid residue in a protein to adopt an Alpha-helical or a coil conformation, in polar and nonpolar media. A second objective is to assess the influence of neighbor (and ultimately more long-range) interactions on such helix-forming tendencies. The experimental values of s and o will then be used to provide information about the conformational properties of proteins. The parameters themselves will be obtained by studying the helix-coil transition of random copolymers of two types of amino acid, a host (whose s and o values are known) and a guest (whose s and o values are to be determined). Random copolymers of varying chain length and of varying composition of the host and guest residues will be synthesized and fractionated; melting data will be obtained for these fractions, in both water (at high and low pH) and organic solvents. Similar experiments will be carried out with multi-component random copolymers. Appropriate theory is available for analyzing such experimental data. We will also examine the acid-base equilibria, in those copolymers containing amino acids with ionizable side chains, to obtain direct information on the influence of near-neighbor interactions on pK's. Similar studies will be carried out to determine the intrinsic tendencies of the 20 naturally occurring amino acids to form Beta structures in water. The data to be acquired here constitute an essential ingredient of a protein-folding algorithm, and will lead to insight as to how various intramolecular interactions determine the conformation of a native protein. Such information will provide an understanding of the importance of conformation in molecular diseases, e.g. of the role of an amino acid substitution in producing sickle cell hemoglobin.